Small case series have suggested increased incident cancer in patients with sickle cell disease (SCD), which, if confirmed, might affect cancer surveillance recommendations for these patients. Experimental data have linked chronic inflammation and high cellular turnover, both hallmarks of SCD, to increased risk of malignancy. Because increased incident cancer in SCD has important implications for management of these patients, it is necessary to rigorously test this finding in a large patient cohort. We propose to determine the incidence of cancer in Californians with SCD by linking two existing databases created for surveillance purposes?the California Cancer Registry (CCR) and the California Office of Statewide Health Planning and Development (OSHPD) Patient Discharge and Emergency Department Utilization. We estimate between 6,000-8,000 cases with SCD will be found. We will test the hypothesis that cancer risk is increased in the SCD population through the following specific aims. Specific Aim 1: Determine the standardized incidence ratio of cancer amongst Californians with SCD. The SCD cohort will be created using a search algorithm informed by the Registry and Surveillance System for Hemoglobinopathies (RuSH) project, a collaboration between the Centers for Disease Control and Prevention (CDC) and the National Heart Lung and Blood Institute. The algorithm has been validated by the CDC-funded Public Health Research, Surveillance and Epidemiology in Hemoglobinopathies (PHRESH) study. Specific Aim 2: Describe the epidemiology of cancer in patients with SCD, including types of malignancies, demographics, and potential risk factors associated with incident cancer. These data will have significant impact on our knowledge of the complications of SCD, and important implications for cancer screening as survival for patients with SCD improves. It will also provide insight into how SCD affects cancer-specific survival. Assessment of potential risk factors associated with development of malignancy in the SCD population that can be pursued in future, more mechanistic studies. An example might be an association between malignancy and the number of transfusions, severity of SCD as measured by frequency of admissions or other complications, or co-morbidities such as autoimmune disease. These results will also serve as preliminary data for an R01 proposal that would determine the epidemiology of cancer and risk factors for cancer in patients with SCD from the seven states that participated in the RuSH project (California, Georgia, Florida, Michigan, North Carolina, New York, and Pennsylvania).